The goal of this research is to understand the mechanisms underlying control of the cell replication patterns which characterize normal vs. transformed human fibroblastic cells, in vitro. Specific proposals are to be explored concerning the interaction of serum mitogens and other auxiliary factors, with the cell surface. A new model for a membrane generated second messenger as a modulator of normal human fibroblast replication is suggested, and a program for testing it defined. Comparison of normal human fibroblasts with their virus- transformed and spontaneously transformed counterparts, in regard to these mechanisms, will be made in an attempt to elucidate wherein lie the disorders associated with transformation in the normal chain of control. The principal methods to be used will be tissue culture, biochemistry, and electron microscopy.